title: A tension-induced mechanotransduction pathway promotes epithelial morphogenesis.
abstract: Mechanotransduction refers to the transformation of physical forces into chemical signals. It generally involves stretch-sensitive channels or conformational change of cytoskeleton-associated proteins. Mechanotransduction is crucial for the physiology of several organs and for cell migration. The extent to which mechanical inputs contribute to development, and how they do this, remains poorly defined. Here we show that a mechanotransduction pathway operates between the body-wall muscles of Caenorhabditis elegans and the epidermis. This pathway involves, in addition to a Rac GTPase, three signalling proteins found at the hemidesmosome: p21-activated kinase (PAK-1), the adaptor GIT-1 and its partner PIX-1. The phosphorylation of intermediate filaments is one output of this pathway. Tension exerted by adjacent muscles or externally exerted mechanical pressure maintains GIT-1 at hemidesmosomes and stimulates PAK-1 activity through PIX-1 and Rac. This pathway promotes the maturation of a hemidesmosome into a junction that can resist mechanical stress and contributes to coordinating the morphogenesis of epidermal and muscle tissues. Our findings suggest that the C. elegans hemidesmosome is not only an attachment structure, but also a mechanosensor that responds to tension by triggering signalling processes. We suggest that similar pathways could promote epithelial morphogenesis or wound healing in other organisms in which epithelial cells adhere to tension-generating contractile cells.
authors.affiliation: Development and Stem Cells Program, IGBMC, CNRS (UMR7104), INSERM (U964), Université de Strasbourg, 1 rue Laurent Fries, BP10142, 67400 Illkirch, France.
authors.forename: Huimin
authors.initials: H
authors.lastname: Zhang
authors.forename: Frédéric
authors.initials: F
authors.lastname: Landmann
authors.forename: Hala
authors.initials: H
authors.lastname: Zahreddine
authors.forename: David
authors.initials: D
authors.lastname: Rodriguez
authors.forename: Marc
authors.initials: M
authors.lastname: Koch
authors.forename: Michel
authors.initials: M
authors.lastname: Labouesse
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology* / Q000201:enzymology / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000196:embryology*; D022002:Hemidesmosomes / Q000378:metabolism; D007382:Intermediate Filaments / Q000378:metabolism; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D009024:Morphogenesis; D009119:Muscle Contraction / Q000502:physiology*; D009132:Muscles / Q000196:embryology / Q000502:physiology; D010641:Phenotype; D010766:Phosphorylation; D015398:Signal Transduction; D054462:p21-Activated Kinases / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; C534514:GIT-1 protein, C elegans; C534515:PIX-1 protein, C elegans; C101878:pak-1 protein, C elegans; D054462:p21-Activated Kinases